European Patent Publication Number 627,406 (A1), the relevant disclosure of which is incorporated herein by reference, discloses a series of 2-amino-2-[2-(4-C2-20-alkyl-phenyl)ethyl]propane-1,3-diol compounds. On the basis of observed activity, the compounds have been found to be useful as immunosuppressants. Accordingly, the compounds may be useful in the treatment or prevention of various autoimmune conditions, including multiple sclerosis. A particular compound in this class is FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol; fingolimod), which may be obtained in the form of the free base or as a hydrochloride salt. The structure of FTY720 is shown below:
FTY720 is known to be metabolised in vivo by three pathways. The three pathways concerned are: (i) reversible phosphorylation to FTY720-phosphate (FTY720-P), (ii) oxidation at the terminal methyl group of the octyl chain to yield the octanoic acid derivative, followed by successive loss of two carbon units though β-oxidation to give the hexanoic acid, butyric acid and acetic acid derivatives, and (iii) formation of non-polar ceramide derivatives (Zollinger et al. Abstracts from the 10th European Regional ISSX Meeting, Drug Metabolism Reviews, 2008, 40:S1, page 125).
Certain ceramide analogues of FTY720 have now been identified and characterised. These ceramide analogues are potential new agents for treatment of autoimmune diseases, such as multiple sclerosis.